第三版心肌梗死定義英文版

ClinicalBiochemistryVolume46,Issues1-2,January2013,Pages1-4ThirdUniversalDefinitionofMyocardialInfarctionAllanS.Jaffe,IntroductionTheThirdUniversalDefinitionofMyocardialInfarction(Ml)wasrecentlypublishedconjointlybythemajorcardiologyorganizationsthroughouttheworldandinthejournalsoftheWorldHealthOrganization(WHO).Thisdefinitionbuildsontwoprevioustwoiterationswhichweredevelopedtomakethediagnosisofmyocardialinfarction(MI)moreconsistent.Theeffortsstartedoriginallyin1999intheconferenceinNicestimulatedbytheinnovationofDr.KristianThygesenandDr.JosephAlbertwhohadrecognizedthisproblemandwhodevelopedataskforcejointlysponsoredbytheACC(AmericanCollegeofCardiology)andtheESC(EuropeanSocietyofCardiology)toattempttostandardizethedefinitionofMI[1].ThismajorstepledtothefirstdocumentwhichmovedthefieldfromtheepidemiologicallyorienteddefinitionofMIwhichhadbeendevelopedbytheWHOtotracktheincidenceofcoronarydiseaseandthereforewasorientedtowardsspecificitytoamoreclinicallyorienteddefinitionwhichreliedonbiomarkersasakeyfeatureofthediagnosis.Thisresultedinaparadigmshiftwherethediagnosisrequireddocumentationofmyocardialnecrosiswithbiomarkersandespeciallycardiactroponin(cTn)whichwasemergingatthe廿meintheproperclinicalsituation.Aseconditerationin2007[2]updatedtheguidelinesandthe2012definitionrefinesthedefinitionstillfurtherparticularlyasitrelatestobiomarkers[3]whichhaveinthepastdecadebecomeprogressivelymoreandmoresensitive.Intrinsically,increasesinsensitivityofthissorttendtoresultinadiminutionofspecificitysinceincreasinglysensitivemeasurementsoftenunmasknewetiologiesforinthisinstance,elevationsofthesesensitivecTnbiomarkers.Areasofthe2012definitionthatremainsimportantbutunchangedThedefinitionofMIfromthepathologiccircumstanceobviouslyisnotgoingtochange.Thedefinitionmandatesthefindingofcardiomyocytenecrosisdefinedpathologicallyduetomyocardialischemia.However,theclinicaldefinitionsincepathologyisnotreadilyavailabletoguideclinicalcarereliesonasurrogatemarkerforcardiacinjury;i.e.,cardiacbiomarkersandparticularly,cTn.Asinpreviousiterations,cTnisthebiomarkerofchoiceandstronglypreferredfortheoverallguidelinesaswellasforeachspecificguideline.ThedefinitionofMlfromtheclinicalperspectivehasnotchangedsubstantively.Itrequiresdetectionofariseand/orafallofacardiacbiomarker,preferablycTn,withatleastonevalueabovethe99thpercentilereferencelimitintheappropriateclinicalsetting(seeTable1forcriteria).ThereareadditionaltypesofMIwhichwillbecoveredsubsequentlybuttheguidelinesrelyheavilyonclinicalsignsorsymptoms,aclinicalsituationwhereischemiaissuspectedevenifsignsandsymptomsareabsentorimaginginformationsuggestiveofischemiainthepresenceofachangingpatternofelevatedbiomarkers.Table1.Criteriaforacutemyocardialinfarction(ThirdUniversalDefinitionofMyocardialInfarction).ADetectionofariseand/orafallofcardiacbiomarkervalues(preferablycardiactroponin(cTn))withatleastonevalueabovethe99thpercentileupperreferencelimit(URL)andatleastoneofthefollowing:AIschemicsymptomsAECGchangesofnewischemia(newST-TchangesornewLBBB)ADevelopmentofpathologicQwavesintheECGAImagingevidenceofnewlossofviablemyocardiumornewregionalwallmotionabnormalityAIdentificationofanintracoronarythrombusbyangiographyorautopsyFull-sizetableTableoptionsThemetricsfortheuseofthesebiomarkersremainthesame.Oneneedsavalueabovethe99thpercentileoftheupperreferencelimitwitharisingand/orafallingpatternofvalues.However,ascTnassaysensitivityhasimproved,theabilitytoconsistentlyoperationalizethesecriteriahasbecomemoreproblematicaswillbediscussedbelow.Thedocumentalsorecognizesavarietyofspecialclinicalcircumstanceswhichrequireuniquehandling.Someofthesearerelatedtocardiacproceduressuchaspercutaneousinterventions(PCI)orcoronaryarterybypassgraft(CABG)surgerybutotherstonovelproceduresthatarebeingdevelopedsuchastranscutaneousaorticvalveinterventions(TAVI).Thedocumentdiscussesaswellsubsetsofpatientswhoarecriticallyill,thosewithheartfailure,andthoseundergoingnon-cardiacsurgeryaswell.Theseclassificationsarenotnewfromthe2007documentbutareconsideredingreaterdetail.IssuesrelatedtobiomarkersAsinthepast,cTnisthemarkerofchoiceandariseand/orafallinvaluesisnecessarytodefineanacuteeventsuchasMI.Itisrecognizedthatthereissometensionabouthowonedefinesthe99thpercentile.Itisassaydependentandisoftendefinedbasedonconveniencesamples.Therefore,thereisconcernthatperhapstheyarenotasreliableasifthesamplepopulationsweremoreintensivelystudied[4].Thevaluesfortheseassaysshouldbeexpressedinng/Lsothattheyarewholenumbersbecauseasassaysbecomemorecomplicatedandmoresensitive,thenumberofzeroscouldleadtoclinicaldysfunction.TheassaysshouldbepreciseandthedocumentprefersassaysthathaveexcellentprecisionwithaCVof10%orlessofthe99thpercentiletoallowdetectionofchangingvalues.However,thedocumentallowsforassayswithCVsupto20%tobeused[5].Italsoisnotedthatanalyticandpre-analyticproblemscanbeproblematicandleadtofalse-positiveandfalse-negativevaluesespeciallywithmoresensitiveassays.Itisalsorecommendedthatsexdependentvaluesmaybeusedwithhighsensitivityassays.Samplingshouldbedoneat0,3,and6handlaterifadditionalepisodesoccurorifthe廿mingoftheinitialsymptomsisunclear.Thediagnosisrequiresarisingandafallingpatternwhichisessentialtodifferentiateelevationsthatareacutefromthosethatarechronicandassociatedwithstructuralheartdiseasesuchaspatientswithrenalfailure,heartfailure,leftventricularhypertrophy,andthelike.Itisrecognizedthatoneneedstobecarefulbecauseat廿mesonecouldpresentsufficientlylateastomissanelevatedvalueorcouldbenearthe廿meofpeakvaluesatwhichpointin廿meonecouldbelievethatachangehadnotoccurredwhensimplythevaluesweresimilaronbothsidesofthepeak.ItisrecognizedandallowedthattheremaybecircumstancesinwhichcardiacinjurycouldbepresentbutnotmeetthediagnosisofMIbecauseitisnotintheappropriatesettingordoesnotmanifestariseandafallandtherearealargenumberofsuchsituationsinwhichadiagnosisofcardiacinjurymaybemoreappropriatethanthediagnosisofacuteMI(seeTable2).Table2.Elevationsofcardiactroponinvaluesbecauseofmyocardialinjury(ThirdUniversalDefinitionofMyocardialInfarction).AInjuryrelatedtoprimarymyocardialischemia(MItype1;i.e.,plaguerupture,intraluminalcoronaryarterythrombusformation)AInjuryrelatedtosupply/demandimbalanceofmyocardialischemia(MItype2;i.e.,tachy-/brady-arrhythmias,aorticdissection,orsevereaorticvalvedisease,hypertrophiccardiomyopathy,cardiogenicorsepticClassificationofMIsClassificationofMIsClassificationofMIsClassificationofMIsshock,severerespiratoryfailure,severeanemia,hypertensionwithorwithoutLVH,coronaryspasm,coronaryembolismorvasculitis,coronaryendothelialdysfunctionwithoutsignificantCAD)AInjurynotrelatedtomyocardialischemia(i.e.,cardiaccontusion,surgery,ablation,pacing,defibrillatorshocks,rhabdomyolysiswithcardiacinvolvement,myocarditis,cardiotoxicagents)AMultifactorialorindeterminatemyocardialinjury(i.e.,heartfailure,stress(takotsubo)cardiomyopathy,severepulmonaryembolismorpulmonaryhypertension,sepsisandcriticallyillpatients,renalfailure,severeacuteneurological(e.g.,stroke)infiltrativediseases(e.g.,amyloidosis),strenuousexercise)OperationalizingchangeincTnvaluesiscomplexandassaydependent.Itshouldbeclearthatgivenpreviouswaysofdiagnosinginfarctionhaveoftennotrequiredchangesovertimethatasonestartstoimplementthesechanges,onewillhavedifferencesinbothsensitivityandspecificity[6].Infact,mostofthedatainthisareasuggeststhattheuseofdeltachangecriteriaimprovesspecificitybutatthecostofsensitivity.Therearemultiplereasonswhythiscouldbethecase.Thefirstisthatitmaybethattherearepatientsbeingdiagnosedwithacuteinfarctionwhodonothavearisingandafallingpatternbasedonclinicaljudgmentsinceonecanhaveacutelookingplaqueseveninpatientswithstablecoronaryarterydisease[7].Asecondpotentialissuerelatestothesituationwherethereisvariationincoronaryarteryperfusion.Biomarkerreleaseisflowdependentandtheconsequenceofthatisthattheremaywellbecircumstanceswithclosedvesselswhereittakesmuchlongerfortheegressofmarkertoreachthecirculationthaninothers.Thus,theideaofshortperiodsofoneortwohoursampling廿meslookingforchangemaybeinadequate.Therealsoareissuesrelatedtothespontaneouschangethatcanoccur.Thishasbeentermedbiologicalvariationandclearlyismuchmoresubstantialthanjustthevariabilityassociatedwiththeimprecisionoftheassays[8].Nonetheless,itisclearthereissomeoverlapbetweenthevaluesthatonebelievesareassociatedwithpatientswithMIandthevaluesthatareconsideredpartofthespontaneousbiologicalvariation[9].Inaddition,theoptimalvaluestousewitheachassayarenotclear.OnecouldcalculateanROCcurvewhichmanylaboratoriansareenamoredofdoingandpickthevaluethatclassifiesthemostpatientscorrectly.However,thismaynotbewhatcliniciansneed.Cardiologistswantrelativelyhighspecificitytoavoidunnecessaryproceduresinpatientswhoarenotatrisk,whereasemergencydepartmentphysiciansoftenwantmoresensitivecriteriasothattheydonotinadvertentlydischargepatientswhoareatrisk[10].Thebalancebetweenthesetwoneedstobefoundateachinstitutionallevel.Thus,thecomplexityofthisissue,withhigh-sensitivityassays,needstobediscussedateachlocalsiteandadjudicatedonacasebycasebyassaybasis.TherearemultiplereasonswhycTncouldbeelevatedthatneedtobedistinguishedfromMl.OnecouldhavearisingandafallingpatternofcTnduetosepsisorpulmonaryembolism,oracuteheartfailurewithmyocardialstretch;noneofwhichwouldbeassociated,norshouldbeconsideredthesameasMI.Inaddition,therearetypesofMIsaswellanditmaywellbeofsomeimportaneetodistinguishthetypesasthecareoftheseindividualsmaybedifferent.ThetaskforcerecognizedmultipletypesofacuteMl[3].Theydefinetype1whichmanyhavecalledthesocalled“wild”typeasanepisodeassociatedwithplaqueruptureandspontaneousinnature.Thus,thesepatientsmostoftenpresentafteranepisodeofchestdiscomfortoftenwithECGchanges,elevatedbiomarkers,andinthestudiesofsuchpatientsitisclearthathavinganelevatedcTnindicatesabeneficialresponsetoanaggressivestrategywithanticoagulationandtheuseofllb/lllaagentsandearlyinvasivestrategy[11].Socalledtype2Mlsarelesstypical.Theyoftenoccurinpatientswhohavefixedatheroscleroticdiseasewhodevelopedtachycardia,hyper-orhypotension,orinindividualswhohaveabnormalitiesincoronaryvasomotionsuchthattheydonotimproveincreasedcoronarybloodflowinresponsetostressorhaveovertvasospasm.Sucheventscanevenoccurinsomeindividualswhosecoronaryarteriesaretotallynormalbutwhohavesuchseveresupplydemandimbalaneeduetoextremetachycardia,hyper-orhypotension.Thesescenarioscanbecomecomplex.Onecouldsuggestthatthereisacontinuumbetweenmyocardialinjurywhichmightbediagnosed,forexample,inayoungpersonwithtachycardiawhohadanelevatedcTnthanwhowastotallyasymptomatic,toasimilarpatientwhomighthavemoretypicalchestpainwhomightbecalledatype1Ml,toanindividualwhomighthavevaguesymptomsthataredifficulttoclassifyinwhomadiagnosisoftype2Mlmightbemade.ThisisanareawhereclinicaljudgmentwillbeimportantforcliniciansbutitshouldbeclearthatsolitaryelevationofcTnevenwitharisingandafallingpatterndoesnotmandateadiagnosisofMl.Thesedistinctionsaremademoredifficultbythefactthatincertaincircumstancessuchastheelderly,thediabetic,andpatientswhoarepostoperativeclassicfindingsmaynotbeobserved.Type3MlsubsumesthatcircumstaneewherethereisapatientwithaclassicMldocumentedeitherbyelectrocardiographyorangiographywherethebiomarkershavenotbeenobtainedorhavenothadsufficient廿metobeelevated.Thisisrarelyaproblemexceptinthosepatientswhosuccumbataveryearly廿meduringtheprocess.TherealsoaremyocardialinfarctionsassociatedwithrevascularizationproceduressuchasPClorCABG.Thesearecomplexandwillbecoveredbelow.ElectrocardiographicchangesTheelectrocardiographicchangesthatshouldbeobservedfordidnotchangemarkedlybutlookingforevideneeofcircumflexcoronaryarteryischemiaisemphasized.Posteriorleads(V-V)shouldberecordedinpatientswhomayhave79circumflexinvolvement.ThismaybesuspectedifthereisSTsegmentdepressioninV1V3.TheECGcriteriaforacuteMlandcommonECGpitfallsindiagnosinginfarctionaredetailedintheThirdUniversalDefinitionofMyocardialInfarction[3].PeriproceduralmyocardialinfarctionsThisisanareaofintensecontroversy.Itisclearthatmyocardialinjurycanoccurafterpercutaneousprocedures.Thiscanbeduetoemboli,whethertheyareaclotofatherosclerotic,occlusionofasidebranch,orsimplyprolongedischemia.Whathasbeenproblematichasbeentheabilitytoknowforsurethattheseeventsareassociatedwithanadverseprognosis[12].Thecriteriaprovideddonotattempttomakethatdistinctionsincesuchadistinctionrequiresoutcomedata.Thethoughtwiththatisthatformanysuchelevations,elevationspriortotheprocedurearepresentbuthavebeenignored[12].Indeedinrecentmeta-analysis,notonestudythatclaimedtohaveanormalbaselinehadsuchabaseline.Therefore,theproponentsofthisparticularpointofviewwouldarguethatthereisrarelyprognosticsignificanee.Ifso,thequestionarisesastowhetherornotdiagnosingthesepatientswithacuteMIisofvalue.Theopposingviewisthatpriorstudies,particularlydonewithlesssensitivemarkerswhereonecouldignorethebaselinechangesbecausemarkerslikeCK-MBwereinsensitiveanddidnotdetectverymanysuchelevationssuggestedthattherewasprognosticsignificancetotheseevents.GiventhetaskforcehasmovedstronglytowardacTnorientedstructureanddidnothaveto,nordid,dwellontheissueofprognosticsignificance,thequestionthenwasviewedashowtodefineadistinctionbetweenthecardiacinjurythatmighthaveledtotheprocedureandsomesortofadditionalinsultcausedbytheprocedureitself.ThetaskforcethendecidedtomandatetheneedforanormalcTnvalueordocumentationofastableorafallingpatternatbaselineandthentorelyona5foldelevationofcTnwhentherewasaclearcutabnormalityinducedbytheprocedureitselformarkedsymptomsoccurred.Thecriteriausespreviouslyofathreefoldwasincreasedtofivefoldalongwiththeseancillarycriteriagiventheincreaseinassaysensitivitythathasoccurredsince2007butitshouldbeclearthatgiventheheterogeneityofpresentdaycardiactroponinassaysthatthiswillbeamovingtargetdependingupontheassaythatoneutilizesinanygivensituation.AsimilarstatementcanbemadeforCABG.Unfortunately,giventheheterogeneityofassays,thereisnosinglecutoffvaluethatcanbeutilized.However,itisclearthatindividualswhostartwithanelevatedcTnpreoperativelyelaboratemorecTn[3].Thus,anormalbaselinevalueisimportantforcomparativeinformation.ItisalsoclearthatthemorecTnthatiselaborated,themoreadversetheprognosis;thus,makingmanymorecomfortablewiththisdiagnosisthanwiththepost-PCIdiagnosis[13].However,therealsoisanobligatoryamountofinjurythatisindigenoustothecardiacsurgicalprocedureandthequestionishowmuchshouldbeorshouldnotbeincluded.AnarbitrarydecisionwasmadetosuggestthataboveatenfoldincreasefromtheURLvalueforanygivencTnassayshouldbeconsideredabnormalandleadtoinvestigationlookingtoseeiftheadditionalcriteriawerepresent.Thesecouldbeprovidedbyimagingorbytheelectrocardiogram.NovelcircumstancesSeveralothercircumstancesarerecognizedintheguidelinesthatareofrelevanee.Forexample,anyproceduredoneontheheartislikelytocauseelevationsofcTn.Therefore,transcatheteraorticvalveimplantations,thesocalledTAVIormitralclipproceduresarelikelytocausesuchcardiacinjury.ThetaskforcesuggestedthatthecriteriaforCABGbeappliedinthatcircumstanee.Innon-cardiacsurgicalprocedures,thereoftenarecTnelevations.Manyoftheseappeartobethesocalledtype2eventsalthoughdefinitiveinformationinthisareaislackinganditisnotclearthatwehavedefinedwellenoughtheappropriateclinicalcriteriatodistinguishtype1andtype2MI[3].Nonetheless,itappearsthatatleastbasedonanearlierdataandvascularsurgerypatientsthatpatientsoftenhaveabnormalitiesinthesupplyanddemandthatcanbedocumented.Ithasbeenshown[14]thattachycardia,hypotension,orhypertensionpostoperativelyisoftenassociatedwithST干wavechangesandsubsequentelevationincTnandtheadverseprognosisareknowntobeassociatedtosuchelevations.However,thepathologicliteraturewouldsuggest,andthisiswhyoneneedstobecautiousinthisarea,thatthoseeventsthatleadtomortalityoftenareassociatedwithplaqueruptureandmaybemoretype1events[15].Thus,thereisstillambiguityaboutexactlywhattypesofinfarctionsmightexistandthereforethecriteriaarehighlynuancedinthatregard.Similarstatementscanbemadeaboutpatientswhoarecriticallyillwhomayhaveelevationsforavarietyofreasons,someofwhichhavenothingtodowiththesupplydemandimbalaneeandsomeofwhichdo.SomeoftheelevationsincTncouldberelatedtothetoxiceffectsofthedisease(sepsisandheatshockproteinsand/orTNF)orofmedicationsthatarebeingusedtherapeutically[16].Whatissuggestedbythetaskforceisthattheclinicianneedstodevelophisorherownsenseofwhentheseelevationsareduetoischemiaandanimbalaneebetweenmyocardialoxygensupplyanddemandandthenonecandiagnosethatepisodeasatype2MI.Intheabseneeofsuchadiagnosis,onewouldsuggestthepreseneeofcardiacinjuryduetowhateverpathophysiologyisthoughttobepresent.Heartfailureperhapsisoneofthosemorecommonsituationswherethisissuemayarise.Manypatientshaveheartfailureduetoischemicheartdisease.However,therealsoarenon-ischemicmechanismsforthecTnreleaseincludingacutemyocardialstretch[17]sothetaskforcetookaverycarefullookandsuggestedthatalthoughsomeelevationscouldbeduetoacuteischemia,thatthevastmajoritymightwellbeconsiderednottobeduetoacuteinfarction.Again,thisisanareawhereclinicaljudgmentislikelytobeessential.Clinicaltrialsandsocietalissuesoo|5.o5.ooViewRecordinScopusoViewRecordinScopuso2.o2.ItwasacknowledgedintheguidelinesthattheimplementationofthecriteriasuggestedforthediagnosisofMlcouldcausesubstantialdifficultiesbothforpatientsandforthosewhoaredoingclinicaltrials.ThediagnosisofMIcarrieswithitsubstantialnegativeconsequencesandcliniciansshouldbeawareandsensitivetothatissuewhentheyaremakingthisdiagnosis.Inaddition,clinicaltrialgroupsmayhavedifficultyat廿mescollectingtheidealinformationtoemploythecriteriaproposed.Theirabilitytocomeascloseaspossiblehowevertomoreclearlymimictherealworldofclinicalcardiologywillbeimportantifthosetrialsaretohaverealapplicabilitytotheeverydaypatient.Nonetheless,itisclearthattheremaybe廿meswhenresourcelimitationsand/orcircumstancemaketotaladherenceimpossible.ConclusionThe2012guidelinesexpandonthecriteriapreviouslyestablishedandamplifyonthecriteria.However,itisclearthatasadditionaldataaredeveloped,theseguidelinesareapttochangestillfurther.DisclosuresDr.Jaffehasorpresentlyconsultsformostofthemajordiagnosticcompanies.References1.o[1]oTheJointEuropeanSocietyofCardiology/AmericanCollegeofCardiologyCommitteeoMyocardialinfarctionredefined—aconsensusdocumentoftheJointEuropeanSocietyofCardiology/AmericanCollegeofCardiologyCommitteefortheredefinitionofmyocardialinfarctionooJAmCollCardiol,36(2000),pp.959一969

o[2]oK.Thygesen,J.S.Alpert,H.D.WhiteoJointESC/ACCF/AHA/WHFtaskforcefortheredefinitionofmyocardialinfarction.UniversaldefinitionofmyocardialinfarctionooCirculation,116(2007),pp.2634-2653ooViewRecordinScopuso|FullTextviaCrossRefo|Citingarticles(1445)o3.eto[3]etoK.Thygesen,J.S.Alpert,A.S.Jaffe,M.L.Simoons,B.R.Chaitman,H.D.White,al.oThirdUniversalDefinitionofMyocardialInfarctionooEurHeartJ,33(2012),pp.2551-2567oFullTextviaCrossRefo1Citingarticles(476)o4.o[4]oP.O.Collinson,Y.M.Heung,D.Gaze,F.Boa,R.Senior,R.Christensonetal.oInflueneeofpopulationselectiononthe99thpercentilerefereneevalueforcardiactroponinassaysooClinChem,58(2012),pp.219-25ooViewRecordinScopuso1FullTextviaCrossRefo1Citingarticles(77)oo[5]oA.S.Jaffe,F.S.Apple,D.A.Morrow,B.Lindahl,H.A.KatusBeingrationalabout(im)precision:astatementfromtheBiochemistrySubcommitteeoftheJointEuropeanSocietyofCardiology/AmericanCollegeofCardiologyFoundation/AmericanHeartAssociation/WorldHeartFederationtaskforceforthedefinitionofmyocardialinfarctionooClinChem,56(2010),pp.941一943ooViewRecordinScopuso|FullTextviaCrossRefoo6.o[6]oS.F.Aldous,C.M.Florkowski,I.G.Crozier,J.Elliott,P.George,J.G.Lainchbury,etal.oComparisonofhighsensitivityandcontemporarytroponinassaysfortheearlydetectionofacutemyocardialinfarctionintheemergencydepartmentooAnnClinBiochem,48(2011),pp.241-248ooo|oo|FullTextviaCrossRefoo7.o[7]oG.Korosoglou,S.Lehrke,D.Mueller,W.Hosch,H.U.Kauczor,P.M.Humpert,etal.oDeterminantsoftroponinreleaseinpatientswithstablecoronaryarterydisease:insightsfromCTangiographycharacteristicsofatheroscleroticplaqueooHeart,97(2011),pp.823-31ooViewRecordinScopuso|FullTextviaCrossRefo|Citingarticles(75)o&o[8]oF.S.Apple,PO.CollinsonooooIFCCtaskforceonclinicalapplicationsofcardiacbiomarkers.Analyticalcharacteristicsofhigh-sensitivitycardiactroponinassaysooClinChem,58(2012),pp.54-61ooViewRecordinScopusoIFullTextviaCrossRefoo9.o[9]oO.Hammarsten,M.L.Fu,R.Sigurjonsdottir